When bowel surface area is insufficient to absorb nutrients, treatment is typically parenteral nutrition to boost nutrient intake, and countering problems of anaemia, gall and kidney stones
If a person has insufficient bowel surface area to absorb nutrients, symptoms can range from diarrhoea to fatigue, leg oedema and weight loss. This commonly occurs when the small intestine is surgically reduced, or as a result of Crohn’s disease or a birth defect. Treatment is typically parenteral nutrition to boost nutrient intake, and countering problems of anaemia, gall and kidney stones.
A new agent from Takeda, teduglutide, is designed to improve intestinal absorption and reduce the need for parenteral nutrition. It is a recombinant analogue of human glucagon-like peptide 2, a natural protein involved in the rehabilitation of the intestinal lining.
In a trial in 16 patients with short bowel syndrome they were given once or twice daily subcutaneous teduglutide doses of 0.03, 0.10 or 0.15mg/kg/day.1 It increased absolute and relative wet weight absorption across the board, and decreased faecal wet weight and faecal energy excretion. It also significantly increased villus height in those patients who had end jejunostomy. The most common side-effects were an enlargement of the stoma nipple, and mild lower leg oedema. Improvements reversed during the drug-free follow-up period.
In a further randomised, placebo-controlled trial, 83 patients with short bowel syndrome were given a 0.05 or 0.10mg/kg/day dose of teduglutide, or placebo, for 24 weeks.2 Parenteral fluids were reduced at four-week intervals if intestinal fluid absorption increased by at least 10%.
They were considered to have responded if they had demonstrated reductions of at least 20% in parenteral volumes from baseline at weeks 20 and 24, and the primary efficacy end point required higher levels and an earlier and longer lasting response. The lower dose was found to be more effective, and three patients could be completely weaned off parenteral support. The incidence of serious adverse events was similar across the treatment and placebo groups.
It has recently been given a positive opinion by EMA’s CHMP under the trade name Revestive. Its potential as a treatment for Crohn’s disease is also being investigated.
1. P.B. Jeppesen et al. Gut 2005, 54, 1224
2. P.B. Jeppesen et al. Gut 2011, 60, 902